1. Technical Field
The present invention concerns a method for producing diagnostic test elements for the detection of analytes in body fluids. The invention additionally concerns diagnostic test elements which have been produced by such a method.
2. General Introduction
The examination of body fluids enables an early and reliable detection of pathological states in clinical diagnostics as well as the selective and well-founded control of physical conditions. Nowadays a few microliters down to less than 1 microliter blood are often all that is required for individual analyses that are specifically directed towards one parameter. In order to collect blood a sterile, sharp lancet is pierced through the skin for example into the finger pad or the earlobe of the person to be examined. This method is especially suitable when the blood sample can be analysed immediately after blood collection.
Carrier-bound rapid tests have become established for the chemical and biochemical analysis of body fluids in laboratories specialized for this purpose and in particular also for use outside permanent laboratories. Based on a specially developed dry chemistry such carrier-bound rapid tests can be carried out simply and in an uncomplicated manner even by laymen despite the often complex reactions involving sensitive reagents. The most prominent example of carrier-bound rapid tests are test strips for determining the blood glucose content in diabetics.
In the diagnostic tests that are used nowadays for the detection of an analyte (e.g. blood glucose) in a body fluid (e.g. blood) the function of lancing to generate a skin opening and the detection function are usually divided among several components e.g. a lancing aid for lancing and generating a drop of blood and an analytical device e.g. a test strip for taking up the drop of blood, passing the blood from the uptake site to the detection area and the detection of an analyte e.g. blood glucose.
Lancets and suitable devices for them which enable blood to be collected in as painless and reliable a manner as possible are offered especially in the field of so-called home-monitoring i.e. in a field where medical laymen themselves carry out simple analyses of the blood and in this case in particular for the regular blood collection by diabetics that has to be carried out several times daily to control the blood glucose concentration. Examples of lancets and lancing aids are the commercially available devices (lancing aids) and lancets Glucolet® from Bayer AG and Softclix® from Roche Diagnostics GmbH. Such lancets and devices are for example the subject matter of WO 98/48695, EP 0,565,970, U.S. Pat. Nos. 4,442,836 or 5,554,166.
The self-determination of blood sugar is nowadays a method that is used world-wide in diabetes monitoring. Blood sugar devices in the prior art such as e.g. Accu-Check Sensor® (from Roche Diagnostics) consist of a measuring device into which a test element (test strip) is inserted. The test strip is contacted with a drop of blood which has previously been collected from a finger pad by means of a lancing aid. The numerous system components (lancet, lancing aid, test strip and measuring device) require a lot of space and give rise to a relatively complex handling. There are now also systems with a higher degree of integration and thus a simpler handling. These for example include Accu Check Compact® (from Roche Diagnostics), the Glucometer Dex (from Bayer Diagnostics) and the Soft-Sense (from Medisense). In the two former systems the test strips are stored in the measuring device and thus provided for measurement.
A next step in miniaturization can for example be achieved by integrating several functions or functional elements in a single diagnostic test element. For example the operating sequence can be considerably simplified by suitably combining the lancing process and sensory analyte concentration detection in one assembly. Such lancing—measuring disposables which are also referred to in the following as integrated test elements are not yet available on the market but are described for example in DE 101 34 650, U.S. Pat. No. 6,572,566, EP 0,199,484 and U.S. Pat No. 6,143,164.
3. State of the Art
The basic problem with the manufacture of the above-mentioned integrated test elements in which the lancing area and detection area are combined in one assembly is that, on the one hand, the lancing area must be sterile since it comes into contact with the skin or penetrates into the body and, on the other hand, the sensitive detection chemistry in the detection area must not be damaged by the manufacturing process.
U.S. Pat. No. 6,520,326 describes for example the sterilization of an integrated test element in which the entire sensor is sterilized and in particular the lancing and also the detection area. It attempts to reduce damage to the detection chemistry in the detection area by a special selection of the detection chemistry.
In DE 101 42 232 several connected lancets in the form of a tape are manufactured and a second tape on which the detection areas are located is produced in parallel. The lancet tape is sterilized, then combined with the second tape and finally the test elements are separated.
The method described in the state of the art U.S. Pat. No. 6,520,326 has the disadvantage that when selecting the detection chemistry it must be ensured that it is insensitive to sterilization. It appears questionable whether such a method can be realized at all and to what extent an adequate performance in particular with regard to sensitivity and reproducibility can be achieved under these circumstances.
In the case of the manufacturing process described in DE 101 42 232 an additional effort is required to produce two parallel tapes and to accurately fit together the lancing area and detection area.
Object
The object of the present invention is to overcome the disadvantages of the prior art as well as the problems mentioned above. In particular it is the object of the present invention to provide a compact integrated diagnostic test element that can be manufactured in high numbers in which the lancing area is sterile and the detection chemistry in the detection area is functional.